A Phase III Randomized Double Blind Study of Letrozole Versus Placebo in Women With Primary Breast Cancer Completing Five or More Years of Adjuvant Tamoxifen

Trial Information

A Phase III Randomized Double Blind Study of Letrozole Versus Placebo in Women With Primary Breast Cancer Completing Five or More Years of Adjuvant Tamoxifen

OBJECTIVES:

Primary

- Compare the disease-free survival and overall survival of postmenopausal women with
primary breast cancer who have completed at least five years of adjuvant aromatase
inhibitor as initial therapy or after tamoxifen treated with letrozole or placebo.

Secondary

- Compare the incidence of contralateral breast cancer in patients treated with these
regimens.

- Evaluate the long-term clinical and laboratory safety of letrozole, in terms of lipid
profile, cardiovascular morbidity and mortality, incidence of bone fractures, change in
bone density, and common toxic effects, in this patient population.

- Compare the quality of life of patients treated with these regimens. Re-randomization

Primary

- Compare disease-free survival of patients who, after receiving at least 4.5 years of
letrozole, are re-randomized to receive an additional 5 years of letrozole vs placebo.

- Arm II: Patients receive oral placebo once daily. In both arms, treatment continues for
5 years in the absence of disease progression or unacceptable toxicity. Patients in arm
II may then be offered oral letrozole once daily for up to 5 years.

Quality of life is assessed at baseline, at 6 months, and then annually for 4.5 years.

- Double-blind, re-randomization:

Patients who complete ≥ 4.5 years of letrozole (arm I) and who did not experience recurrent
disease or new primary breast cancer, including ductal carcinoma in situ, may participate in
the double-blind, placebo-controlled, re-randomization portion of the study. Patients are
stratified according to lymph node status at enrollment (negative vs positive vs unknown),
prior adjuvant chemotherapy (yes vs no), and interval between last dose of letrozole and
re-randomization (<6 months vs 6 months to 2 years). Common genetic single nucleotide
polymorphisms for genes encoding proteins involved in pharmacokinetic and/or pharmacodynamic
pathways for letrozole are analyzed in order to determine if these single nucleotide
polymorphisms contribute to individual variation in toxicity and efficacy of letrozole
therapy.

Quality of life is assessed as during the first randomization.

Patients are followed annually.

PROJECTED ACCRUAL: A total of 4,700 patients will be accrued for this study.

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed primary invasive breast carcinoma resected
at time of original diagnosis

- No ductal carcinoma in situ

- Axillary lymph node negative, positive, or unknown

- No evidence of metastases

- No localized or distant breast cancer recurrence

- Not registered on protocol NCCTG-893052, any other IBCSG protocol, or protocol
SWOG-S9623

Start Date:

Completion Date:

Related Keywords:

Name

Location

We are a Cancer Social Network, Resource Directory & Education Hub supporting all those affected by cancer. knowcancer.com is intended to be solely for informational purposes and should not be a substitute for professional medical advice, diagnosis or treatment.